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Ecological Fitness of Vibrios and the Emergence of Pathogenic Traits

弧菌的生态适应性和致病性状的出现

基本信息

批准号：
7625019
负责人：
Hans Wildschutte
金额：
$ 5.01万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2010-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): It is well established that the acquisition of pathogenicity islands (PAIs) assists the transformation of environmental bacteria to disease causing organisms. Yet, it remains poorly understood what limits or promotes the acquisition of PAIs among genetically similar strains. The O-antigen is a highly diverse and strain-specific structure covering the cell surface of Gram-negative bacteria that has been shown to play important roles in both pathogenesis and survival in the environment. I hypothesize that certain combinations of PAIs and O-antigens provide ecological fitness advantages in specific (micro) habitats (e.g., invertebrate guts, plankton, animal surfaces) and that this predisposes specific groups of strains to evolve towards pathogenicity. Vibrios are Gram-negative bacteria; certain strains infect marine animal and human hosts. Because Vibrios are abundant in marine habitats, these bacteria present ongoing threats to both humans and our national aquaculture. Thus, it is necessary to detect marine environments, which may be reservoirs for emerging pathogens in order to monitor these bacterial populations and predict potential pandemics. The Polz laboratory has isolated thousands of microdiverse Vibrios from defined marine habitats. This strain collection is the most exclusive of its kind and presents an excellent means to investigate the emergence of pathogenicity. My research will utilize this collection, as well as other Vibrios isolated from different marine habitats to: (i) characterize subpopulations of Vibrios based on core gene microdiversity using MLSA and phylogenetic approaches, (ii) determine the frequency that PAIs and virulence genes occur in these environmental Vibrios. Probes will be developed from known Vibrios virulence loci and other Ioci identified from published genomes using bioinformatics methods; these probes will be used to find virulence genetic elements using PCR and Southern blotting techniques, (iii) determine at what level O-antigen diversity co-exists with virulence loci and their correlates to specific environments. The wb* region encode genes that help assemble the O-antigen; this region will be isolated and sequenced to characterize this genetically diverse locus. The frequency and combination of both virulence loci and the wb* region will help determine if certain environments are breeding ground for pathogens. Pathogens infect particular hosts and cause disease. The relevance of this work is to determine if different marine environments are reservoirs for emerging pathogens that pose threat to both humans and commercial aquaculture. Results may lead to insights on how to monitor and predict bacterial outbreaks.

描述（由申请方提供）：已明确，致病岛（PAI）的获得有助于环境细菌转化为致病微生物。然而，它仍然知之甚少是什么限制或促进收购PAI之间的遗传相似的菌株。O-抗原是覆盖革兰氏阴性菌细胞表面的高度多样性和菌株特异性结构，其已被证明在致病和环境中的存活中起重要作用。我假设PAI和O-抗原的某些组合在特定（微）栖息地（例如，无脊椎动物的内脏、浮游生物、动物表面），这使特定的菌株群易于向致病性进化。弧菌是革兰氏阴性细菌;某些菌株感染海洋动物和人类宿主。由于弧菌在海洋栖息地丰富，这些细菌对人类和我们国家的水产养殖业构成持续的威胁。因此，有必要检测海洋环境，这可能是新出现的病原体的水库，以监测这些细菌种群和预测潜在的大流行病。Polz实验室已经从确定的海洋栖息地中分离出数千种微多样性弧菌。该菌株收集是同类中最独特的，并提供了一种研究致病性出现的极好手段。我的研究将利用这个集合，以及从不同的海洋栖息地分离的其他弧菌：（i）使用MLSA和系统发育方法基于核心基因微多样性表征弧菌亚群，（ii）确定PAI和毒力基因在这些环境弧菌中发生的频率。探针将从已知的弧菌毒力基因座和其他Ioci使用生物信息学方法从已发表的基因组中鉴定;这些探针将用于使用PCR和Southern印迹技术发现毒力遗传元件，（iii）确定O-抗原多样性与毒力基因座共存的水平及其与特定环境的相关性。该区域编码有助于组装O-抗原的基因;该区域将被分离和测序以表征该遗传多样性位点。毒力基因座和基因座 * 区域的频率和组合将有助于确定某些环境是否是病原体的滋生地。病原体感染特定的宿主并引起疾病。这项工作的相关性是确定不同的海洋环境是否是对人类和商业水产养殖构成威胁的新兴病原体的储存库。结果可能会导致如何监测和预测细菌爆发的见解。